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<1>
Accession Number
2012550850
Authors
Eren M.N. Aydin S. Ozercan I.H. Dagli A.F.
Institution
(Aydin) Department of Cardiovascular Surgery, Elazig State Hospital,
Elazig, Turkey
(Eren) Department of Cardiovascular Surgery, Medical Faculty of Dicle
University, Diyarbakir, Turkey
(Aydin) Department of Medical Biochemistry and Clinical Biochemistry
(Firat Hormones Research Group), Medical Faculty of Firat University,
23100 Elazig, Turkey
(Ozercan, Dagli) Department of Pathology, Medical Faculty of Firat
University, 23100 Elazig, Turkey
Title
The bioactive peptides salusins and apelin-36 are produced in human
arterial and venous tissues and the changes of their levels during
cardiopulmonary bypass.
Source
Peptides. 37 (2) (pp 233-239), 2012. Date of Publication: October 2012.
Publisher
Elsevier Inc. (360 Park Avenue South, New York NY 10010, United States)
Abstract
This study aimed to examine the effects of CPB on salusin-alpha,
salusin-beta and apelin-36 bioactive peptides in people who are planned to
undergo coronary artery bypass graft (CABG) operation due to coronary
artery disease and to explore whether these peptides are produced in human
aortic, saphenous and arterial tissues. The study included age and BMI
matched 15 patients who underwent CABG operation by CPB. In order to
determine salusin-alpha, salusin-beta and apelin-36 levels, venous blood
samples were collected before induction of anesthesia (T1), before CPB
(T2), 5 min before the removal of cross-clamp (T3), 5 min after the
removal of cross-clamp (T4), upon arrival in the intensive care (T5), at
postoperative 24th hour (T6) and 72nd hour (T7). Salusin and apelin
expressions of the tissues were shown by immunohistochemical method.
Peptide amounts of sera and tissues were measured using ELISA. Salusins
production by vessels occurs in fibroblast cells of the media in the aorta
and smooth muscle cells of the media in the LIMA and saphena. Apelin is
produced by endothelial cells of the intima and fibroblast cells of the
media in the aorta and by smooth muscle cells of the media in the LIMA and
saphena. Changes in the levels of salusin-beta and apelin-36 were
significant during CPB. Salusin-alpha, salusin-beta and apelin-36 are
locally synthesized in the arteries and veins. Salusins and apelin-36
might be important markers in the CPB, and also that salusin-beta was more
specific in comparison to salusin-alpha. 2012 Elsevier Inc.

<2>
Accession Number
22559139
Authors
Wolff B.C. Wadsworth M.E. Wilhelm F.H. Mauss I.B.
Institution
(Wolff, Wadsworth) Department of Psychology, University of Denver, 2155
South Race Street, Denver, CO 80208, United States
(Wilhelm) University of Salzburg, Austria
(Mauss) University of California, Berkeley, United States
Title
Children's vagal regulatory capacity predicts attenuated sympathetic
stress reactivity in a socially supportive context: Evidence for a
protective effect of the vagal system.
Source
Development and Psychopathology. 24 (2) (pp 677-689), 2012. Date of
Publication: May 2012.
Publisher
Cambridge University Press (Shaftesbury Road, Cambridge CB2 2RU, United
Kingdom)
Abstract
Social support and vagal regulatory capacity (VRC), an index of flexible
vagal responses during various types of stress, are linked to attenuated
stress responding and positive health outcomes. Guided by the polyvagal
perspective, we tested whether children's VRC is associated with
attenuated sympathetic nervous system (SNS) stress reactivity in socially
supportive conditions. Sixty-one 4- to 5-year-old children living in
poverty underwent two standardized laboratory stress induction procedures.
Cardiac vagal reactivity (respiratory sinus arrhythmia) to a first set of
stressors (social, cognitive, physical, and emotional) indexed VRC. During
a second set of stressors, participants were randomly assigned to a
supportive or nonsupportive social context, and cardiac sympathetic
reactivity (preejection period) was assessed. We hypothesized VRC would
predict lower SNS stress reactivity, but only in the socially supportive
context. Children with high VRC showed attenuated SNS stress reactivity in
the socially supportive context compared to children with high VRC in the
nonsupportive context and children with low VRC in either context.
Individual differences in VRC predict attenuated SNS stress reactivity in
socially supportive conditions. Understanding how social support and VRC
jointly mitigate SNS stress reactivity may further efforts to prevent
negative health outcomes. Implications for biological sensitivity to
context and differential susceptibility theories are discussed. 2012
Cambridge University Press.

<3>
Accession Number
2012552630
Authors
Savonitto S. Cavallini C. Petronio A.S. Murena E. Antonicelli R. Sacco A.
Steffenino G. Bonechi F. Mossuti E. Manari A. Tolaro S. Toso A. Daniotti
A. Piscione F. Morici N. Cesana B.M. Jori M.C. De Servi S.
Institution
(Savonitto, Manari) Azienda Ospedaliera Santa Maria Nuova, IRCCS, Reggio
Emilia, Italy
(Cavallini) Azienda Ospedaliera Ospedale Santa Maria della Misericordia,
Perugia, Italy
(Petronio) Azienda Ospedaliera Universitaria Pisana, Pisa, Italy
(Murena) Ospedale S. Maria delle Grazie, Pozzuoli, Italy
(Antonicelli) INRCA, Ancona, Italy
(Sacco, Morici) Azienda Ospedaliera Ospedale Niguarda Ca Granda, Milano,
Italy
(Steffenino) Ospedale Santa Croce e Carle, Cuneo, Italy
(Bonechi) Ospedale San Giuseppe, Empoli-Fucecchio, Italy
(Mossuti) Ospedale Umberto i, Siracusa, Italy
(Tolaro) Centro Cuore Morgagni, Pedara, Italy
(Toso) Ospedale Misericordia e Dolce, Prato, Italy
(Daniotti) Ospedale Ca' Foncello, Treviso, Italy
(Piscione) Policlinico Universitario Federico II, Napoli, Italy
(Cesana) Medical Statistics and Biometry, University of Brescia, Brescia,
Italy
(Jori) Mediolanum Cardio Research, Milano, Italy
(De Servi) Ospedale Civile, Legnano, Italy
Title
Early aggressive versus initially conservative treatment in elderly
patients with non-ST-segment elevation acute coronary syndrome: A
randomized controlled trial.
Source
JACC: Cardiovascular Interventions. 5 (9) (pp 906-916), 2012. Date of
Publication: September 2012.
Publisher
Elsevier Inc. (360 Park Avenue South, New York NY 10010, United States)
Abstract
Objectives: This study sought to determine the risk versus benefit ratio
of an early aggressive (EA) approach in elderly patients with
non-ST-segment elevation acute coronary syndromes (NSTEACS). Background:
Elderly patients have been scarcely represented in trials comparing
treatment strategies in NSTEACS. Methods: A total of 313 patients <75
years of age (mean 82 years) with NSTEACS within 48 h from qualifying
symptoms were randomly allocated to an EA strategy (coronary angiography
and, when indicated, revascularization within 72 h) or an initially
conservative (IC) strategy (angiography and revascularization only for
recurrent ischemia). The primary endpoint was the composite of death,
myocardial infarction, disabling stroke, and repeat hospital stay for
cardiovascular causes or severe bleeding within 1 year. Results: During
admission, 88% of the patients in the EA group underwent angiography (55%
revascularization), compared with 29% (23% revascularization) in the IC
group. The primary outcome occurred in 43 patients (27.9%) in the EA group
and 55 (34.6%) in the IC group (hazard ratio [HR]: 0.80; 95% confidence
interval [CI]: 0.53 to 1.19; p = 0.26). The rates of mortality (HR: 0.87;
95% CI: 0.49 to 1.56), myocardial infarction (HR: 0.67; 95% CI: 0.33 to
1.36), and repeat hospital stay (HR: 0.81; 95% CI: 0.45 to 1.46) did not
differ between groups. The primary endpoint was significantly reduced in
patients with elevated troponin on admission (HR: 0.43; 95% CI: 0.23 to
0.80), but not in those with normal troponin (HR: 1.67; 95% CI: 0.75 to
3.70; p for interaction = 0.03). Conclusions: The present study does not
allow a definite conclusion about the benefit of an EA approach when
applied systematically among elderly patients with NSTEACS. The finding of
a significant interaction for the treatment effect according to troponin
status at baseline should be confirmed in a larger size trial. (Italian
Elderly ACS Study; NCT00510185) 2012 American College of Cardiology
Foundation.

<4>
Accession Number
2012552575
Authors
Savarese G. Paolillo S. Costanzo P. D'Amore C. Cecere M. Losco T. Musella
F. Gargiulo P. Marciano C. Perrone-Filardi P.
Institution
(Savarese, Paolillo, Costanzo, D'Amore, Cecere, Losco, Musella, Gargiulo,
Marciano, Perrone-Filardi) Department of Internal Medicine, Cardiovascular
Sciences and Immunology, Federico II University, Via Pansini, 5, I-80131
Naples, Italy
Title
Do changes of 6-minute walk distance predict clinical events in patients
with pulmonary arterial hypertension?: A meta-analysis of 22 randomized
trials.
Source
Journal of the American College of Cardiology. 60 (13) (pp 1192-1201),
2012. Date of Publication: 25 Sep 2012.
Publisher
Elsevier USA (6277 Sea Harbor Drive, Orlando FL 32862 8239, United States)
Abstract
Objectives: The objectives of this study were to verify whether
improvement in 6-min walk distance (6MWD) is associated with clinical
outcome in pulmonary arterial hypertension (PAH). Background: 6MWD is used
as an endpoint to assess the benefit of therapies in PAH. However, whether
changes in 6MWD correlate with clinical outcome is unknown. Methods:
Randomized trials assessing 6MWD in patients with PAH and reporting
clinical endpoints were included in a meta-analysis. The meta-analysis was
performed to assess the influence of treatment on outcomes.
Meta-regression analysis was performed to test the relationship between
6MWD changes and outcomes. Results: Twenty-two trials enrolling 3,112
participants were included. Active treatments led to significant reduction
of all-cause death (odds ratio [OR]: 0.429; 95% confidence interval [CI]:
0.277 to 0.664; p < 0.01), hospitalization for PAH, and/or lung or
heart-lung transplantation (OR: 0.442; 95% CI: 0.309 to 0.632; p < 0.01),
initiation of PAH rescue therapy (OR: 0.555; 95% CI: 0.347 to 0.889; p =
0.01), and composite outcome (OR: 0.400; 95% CI: 0.313 to 0.510; p <
0.01). No relationship between 6MWD changes and outcomes was detected.
Conclusions: In patients with PAH, improvement in 6MWD does not reflect
benefit in clinical outcomes. 2012 American College of Cardiology
Foundation.

<5>
Accession Number
2012559481
Authors
Ozelami Vieira I.B.C. Vieira F.F. Abrao J. Gastaldi A.C.
Institution
(Ozelami Vieira) Universidade Federal do Triangulo Mineiro, Uberaba, MG,
Brazil
(Vieira) Department of Surgery, Universidade Federal do Triangulo Mineiro,
Uberaba, MG, Brazil
(Abrao, Gastaldi) Department of Biomechanics, Medicine and Locomotive
Apparatus Rehabilitation, Faculdade de Medicina de Ribeirao Preto,
Universidade de Sao Paulo, SP, Brazil
Title
Influence of Pleural Drain Insertion in Lung Function of Patients
Undergoing Coronary Artery Bypass Grafting.
Source
Revista Brasileira de Anestesiologia. 62 (5) (pp 696-708), 2012. Date of
Publication: September 2012.
Publisher
Elsevier (P.O. Box 211, Amsterdam 1000 AE, Netherlands)
Abstract
Background and objectives: Longitudinal, prospective, randomized, blinded
Trial to assess the influence of pleural drain (non-toxic PVC) site of
insertion on lung function and postoperative pain of patients undergoing
coronary artery bypass grafting in the first three days post-surgery and
immediately after chest tube removal. Method: Thirty six patients
scheduled for elective myocardial revascularization with cardiopulmonary
bypass (CPB) were randomly allocated into two groups: SX group
(subxiphoid) and IC group (intercostal drain). Spirometry, arterial blood
gases, and pain tests were recorded. Results: Thirty one patients were
selected, 16 in SX group and 15 in IC group. Postoperative (PO)
spirometric values were higher in SX than in IC group (p<0.05), showing
less influence of pleural drain location on breathing. PaO₂ on
the second PO increased significantly in SX group compared with IC group
(p<0.0188). The intensity of pain before and after spirometry was lower in
SX group than in IC group (p<0.005). Spirometric values were significantly
increased in both groups after chest tube removal. Conclusion: Drain with
insertion in the subxiphoid region causes less change in lung function and
discomfort, allowing better recovery of respiratory parameters. 2012
Elsevier Editora Ltda.

<6>
[Use Link to view the full text]
Accession Number
2012560980
Authors
Pretorius M. Murray K.T. Yu C. Byrne J.G. Billings F.T. Petracek M.R.
Greelish J.P. Hoff S.J. Ball S.K. Mishra V. Body S.C. Brown N.J.
Institution
(Pretorius, Billings) Department of Anesthesiology, Vanderbilt University
School of Medicine, Nashville, TN, United States
(Murray) Division of Cardiology, Department of Medicine, Vanderbilt
University School of Medicine, Nashville, TN, United States
(Yu) Department of Biostatistics, Vanderbilt University School of
Medicine, Nashville, TN, United States
(Byrne, Petracek, Hoff, Ball) Department of Cardiac Surgery, Vanderbilt
University School of Medicine, Nashville, TN, United States
(Pretorius, Brown) Division of Clinical Pharmacology, Department of
Medicine, Vanderbilt University School of Medicine, Nashville, TN, United
States
(Greelish) Department of Cardiac Surgery, Columbia University, Gastonia,
NC, United States
(Mishra) Department of Medicine, University of Alabama School of Medicine,
Birmingham, AL, United States
(Body) Department of Anesthesiology, Perioperative and Pain Medicine,
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United
States
Title
Angiotensin-converting enzyme inhibition or mineralocorticoid receptor
blockade do not affect prevalence of atrial fibrillation in patients
undergoing cardiac surgery.
Source
Critical Care Medicine. 40 (10) (pp 2805-2812), 2012. Date of Publication:
October 2012.
Publisher
Lippincott Williams and Wilkins (530 Walnut Street,P O Box 327,
Philadelphia PA 19106-3621, United States)
Abstract
OBJECTIVE: This study tested the hypothesis that interruption of the
renin-angiotensin system with either an angiotensin-converting enzyme
inhibitor or a mineralocorticoid receptor antagonist will decrease the
prevalence of atrial fibrillation after cardiac surgery. DESIGN:
Randomized double-blind placebo-controlled study. SETTING:
University-affiliated hospitals. PATIENTS: Four hundred forty-five adult
patients in normal sinus rhythm undergoing elective cardiac surgery.
INTERVENTIONS: One week to 4 days prior to surgery, patients were
randomized to treatment with placebo, ramipril (2.5mg the first 3 days
followed by 5mg/day, with the dose reduced to 2.5mg/day on the first
postoperative day only), or spironolactone (25mg/day). MEASUREMENTS: The
primary endpoint was the occurrence of electrocardiographically confirmed
postoperative atrial fibrillation. Secondary endpoints included acute
renal failure, hyperkalemia, the prevalence of hypotension, length of
hospital stay, stroke, and death. MAIN RESULTS: The prevalence of atrial
fibrillation was 27.2% in the placebo group, 27.8% in the ramipril group,
and 25.9% in the spironolactone group (p =.95). Patients in the ramipril
(0.7%) or spironolactone (0.7%) group were less likely to develop acute
renal failure than those randomized to placebo (5.4%, p =.006). Patients
in the placebo group tended to be hospitalized longer than those in the
ramipril or spironolactone group (6.8+/-8.2 days vs. 5.7+/-3.2 days and
5.8+/-3.4 days, respectively, p =.08 for the comparison of placebo vs. the
active treatment groups using log-rank test). Compared with patients in
the placebo group, patients in the spironolactone group were extubated
sooner after surgery (576.4+/-761.5 mins vs. 1091.3+/-3067.3 mins, p
=.04). CONCLUSIONS: Neither angiotensin-converting enzyme inhibition nor
mineralocorticoid receptor blockade decreased the primary outcome of
postoperative atrial fibrillation. Treatment with an
angiotensin-converting enzyme inhibitor or mineralocorticoid receptor
antagonist was associated with decreased acute renal failure.
Spironolactone use was also associated with a shorter duration of
mechanical ventilation after surgery. Copyright 2012 by the Society of
Critical Care Medicine and Lippincott Williams and Wilkins.

<7>
Accession Number
2012550283
Authors
Chow W.B. Rosenthal R.A. Merkow R.P. Ko C.Y. Esnaola N.F.
Institution
(Chow, Merkow, Ko) American College of Surgeons, National Surgical Quality
Improvement Program, 633 N Saint Clair St, Chicago, IL 60611-3211, United
States
(Chow, Ko) Department of Surgery, David Geffen School of Medicine at UCLA,
Los Angeles, CA, United States
(Rosenthal) Department of Surgery, Yale School of Medicine, New Haven, CT,
United States
(Esnaola) Department of Surgery, Medical University of South Carolina,
Charleston, SC, United States
Title
Optimal preoperative assessment of the geriatric surgical patient: A best
practices guideline from the American college of surgeons national
surgical quality improvement program and the American geriatrics society.
Source
Journal of the American College of Surgeons. 215 (4) (pp 453-466), 2012.
Date of Publication: October 2012.
Publisher
Elsevier Inc. (360 Park Avenue South, New York NY 10010, United States)

<8>
Accession Number
2012550918
Authors
Arsenault K.A. Paikin J.S. Hirsh J. Dale B. Whitlock R.P. Teoh K. Young E.
Ginsberg J.S. Weitz J.I. Eikelboom J.W.
Institution
(Arsenault) McMaster University, Michael G. DeGroote School of Medicine,
Hamilton, ON, Canada
(Paikin, Hirsh, Ginsberg, Weitz, Eikelboom) Department of Medicine,
McMaster University, Hamilton, ON, Canada
(Whitlock, Teoh) Department of Surgery, McMaster University, Hamilton, ON,
Canada
(Young) Department of Pathology and Molecular Medicine, McMaster
University, Hamilton, ON, Canada
(Hirsh) Population Health Research Institute, Hamilton, ON, Canada
(Dale) University of South Australia, School of Pharmacy and Medical
Sciences, Adelaide, Australia
(Young, Weitz, Eikelboom) Thrombosis and Atherosclerosis Research
Institute, Hamilton, ON, Canada
Title
Subtle differences in commercial heparins can have serious consequences
for cardiopulmonary bypass patients: A randomized controlled trial.
Source
Journal of Thoracic and Cardiovascular Surgery. 144 (4) (pp 944-950.e3),
2012. Date of Publication: October 2012.
Publisher
Mosby Inc. (11830 Westline Industrial Drive, St. Louis MO 63146, United
States)
Abstract
Objective: To compare the potency, reversibility, and perioperative
bleeding risk of Hepalean with those of PPC heparin. Methods: Because in
vitro testing failed to detect differences in the potency or protamine
reversibility of the 2 heparin preparations, we conducted a parallel
group, single-center, double-blind, randomized, controlled trial to
compare the anticoagulant effects of Hepalean to those of PPC heparin in
patients undergoing coronary artery bypass grafting with cardiopulmonary
bypass. Results: From June 1, 2011, to June 30, 2011, we randomly assigned
11 patients to receive PPC heparin and 10 to receive Hepalean. Despite
similar initial doses of heparin, the median initial activated clotting
time was numerically lower in the PPC heparin group than in the Hepalean
group (median, 516.0 seconds; interquartile range, 481.0-633.0; vs median,
584.0 seconds, interquartile range, 520.0-629.0; P = .418). Those given
PPC heparin required a greater total heparin dose (median, 46,000.0 U;
interquartile range, 39,500.0-60,000.0 vs median, 34,500.0 U;
interquartile range, 32,250.0-37,000.0; P = .011) and a greater dose of
heparin per kilogram than those given Hepalean (median, 572.9 U/kg;
interquartile range, 443.0-659.7 vs median, 401.1 U/kg; interquartile
range, 400.0-419.4; P = .003). The key secondary results included an
increased median total protamine dose (median, 600.0 mg; interquartile
range, 550.0-700.0; vs median, 500.0 mg; interquartile range, 425.0-542.5;
P = .026) and a trend toward increased chest tube output within 24 hours
(median, 830.0 mL; interquartile range, 425.0-1135.0; vs median, 702.5 mL;
interquartile range, 550.0-742.5; P = .324). Conclusions: PPC heparin use
was associated with greater heparin and protamine dose requirements than
Hepalean. These findings indicate that heparin preparations are not
interchangeable and suggest that a direct comparison of the potency with
the brand in use is needed if a change is made to ensure that the agents
exert similar anticoagulant effects in vivo.

<9>
Accession Number
2012550917
Authors
Priest J.R. Slee A. Olson A.K. Ledee D. Morrish F. Portman M.A.
Institution
(Priest, Olson, Ledee, Portman) Seattle Children's Hospital, University of
Washington, Seattle Children's Research Institute, 1900 9th Avenue,
Seattle, WA 98101, United States
(Priest) Division of Pediatric Cardiology, Stanford University School of
Medicine, Lucile Packard Children's Hospital, Palo Alto, CA, United States
(Slee) Axio Research, Seattle, WA, United States
(Morrish) Fred Hutchinson Cancer Research Center, Seattle, WA, United
States
Title
Triiodothyronine supplementation and cytokines during cardiopulmonary
bypass in infants and children.
Source
Journal of Thoracic and Cardiovascular Surgery. 144 (4) (pp 938-943.e2),
2012. Date of Publication: October 2012.
Publisher
Mosby Inc. (11830 Westline Industrial Drive, St. Louis MO 63146, United
States)
Abstract
Objective: The Triiodothyronine Supplementation in Infants and Children
Undergoing Cardiopulmonary Bypass (TRICC) study demonstrated a shortened
time to extubation in children younger than 5 months old undergoing
cardiopulmonary bypass for congenital heart surgery with triiodothyronine
supplementation. Cardiopulmonary bypass precipitates a systemic
inflammatory response that affects recovery, and triiodothyronine is
related to cytokine mediators of inflammation. We sought to investigate
the preoperative cytokine levels by age and relationship to the
triiodothyronine levels and to examine the effect of the cytokine levels
on the time to extubation. Methods: We measured 6 cytokines at
preoperative time 0 and 6 and 24 hours after crossclamp removal in 76
subjects. Results: The preoperative cytokine levels were related to both
the triiodothyronine levels and the patient age. The postoperative
cytokine levels were predictive of the triiodothyronine levels at 6, 12,
24, and 72 hours. Preoperative CCL4 was associated with an increased
chance of early extubation. Inclusion of the cytokines did not change the
relationship of triiodothyronine to the time to extubation, and the
postoperative course of interleukin-6 was independently associated with a
decreased chance of early extubation. Conclusions: The preoperative and
postoperative cytokine levels, in particular, interleukin-1beta, showed
complex time-dependent relationships with triiodothyronine. The data
suggest that cytokine-mediated suppression of triiodothyronine plays an
important role in determining the clinical outcome after cardiopulmonary
bypass.

<10>
Accession Number
2012550919
Authors
Vidlund M. Hakanson E. Friberg O. Juhl-Andersen S. Holm J. Vanky F.
Sunnermalm L. Borg J.-O. Sharma R. Svedjeholm R.
Institution
(Vidlund, Friberg, Sunnermalm) Department of Cardiothoracic Surgery and
Cardiothoracic Anesthesia, University Hospital Orebro, Orebro University,
Orebro, Sweden
(Hakanson, Holm, Vanky, Svedjeholm) Division of Cardiovascular Medicine,
Linkoping University Hospital, Linkoping University, Linkoping, Sweden
(Juhl-Andersen, Borg, Sharma) Department of Cardiothoracic Surgery,
Cardiothoracic Anesthesia Blekinge Hospital, Karlskrona, Sweden
Title
GLUTAMICS - A randomized clinical trial on glutamate infusion in 861
patients undergoing surgery for acute coronary syndrome.
Source
Journal of Thoracic and Cardiovascular Surgery. 144 (4) (pp 922-930.e7),
2012. Date of Publication: October 2012.
Publisher
Mosby Inc. (11830 Westline Industrial Drive, St. Louis MO 63146, United
States)
Abstract
Objective: Glutamate has been claimed to protect the heart from ischemia
and to facilitate metabolic and hemodynamic recovery after ischemia. The
GLUTAmate for Metabolic Intervention in Coronary Surgery trial
investigated whether an intravenous glutamate infusion given in
association with surgery for acute coronary syndrome could reduce
mortality and prevent or mitigate myocardial injury and postoperative
heart failure. Methods: In the present prospective, triple-center,
double-blind study, 861 patients undergoing surgery for acute coronary
syndrome were randomly assigned to an intravenous infusion of glutamate (n
= 428) or saline (n = 433) perioperatively. Results: The incidence of the
primary endpoint - a composite of 30-day mortality, perioperative
myocardial infarction, and left ventricular heart failure at weaning from
cardiopulmonary bypass - was 7.3% versus 5.8% (P = .41) in the glutamate
and control groups, respectively. Patients with left ventricular failure
at weaning from cardiopulmonary bypass had a shorter median intensive care
unit stay (25 vs 92 hours; P = .02) if they were treated with glutamate.
In patients with unstable angina (Canadian Cardiovascular Society class
IV) undergoing isolated coronary artery bypass grafting (n = 458), the
incidence of severe circulatory failure according to the prespecified
criteria was significantly lower in the glutamate group (1.3% vs 6.9%; P =
.004). On multivariate analysis, glutamate infusion was associated with a
reduced risk of developing severe circulatory failure (odds ratio, 0.17;
95% confidence interval, 0.04-0.72; P = .02). A relative risk reduction
exceeding 50% for developing severe circulatory failure was seen in most
risk groups undergoing isolated coronary artery bypass grafting, with
those with diabetes a notable exception. Conclusions: The primary endpoint
did not differ significantly between the groups. The secondary outcomes
and post hoc analyses warrant additional studies with regard to the
potential beneficial effect of glutamate on postischemic myocardial
recovery.

<11>
[Use Link to view the full text]
Accession Number
2012555296
Authors
Vieira R.D. Hueb W. Hlatky M. Favarato D. Rezende P.C. Garzillo C.L. Lima
E.G. Soares P.R. Hueb A.C. Pereira A.C. Ramires J.A.F. Filho R.K.
Institution
(Vieira, Hueb, Favarato, Rezende, Garzillo, Lima, Soares, Hueb, Pereira,
Ramires, Filho) Department of Atherosclerosis, Heart Institute of the
University of Sao Paulo, Eneas Carvalho Aguiar 44 AB 114, Sao Paulo,
Brazil
(Hlatky) Stanford University School of Medicine, Stanford, CA, United
States
Title
Cost-effectiveness analysis for surgical, angioplasty, or medical
therapeutics for coronary artery disease: 5-year follow-up of medicine,
angioplasty, or surgery study (MASS) II trial.
Source
Circulation. 126 (11 SUPPL.1) (pp S145-S150), 2012. Date of Publication:
11 Sep 2012.
Publisher
Lippincott Williams and Wilkins (530 Walnut Street,P O Box 327,
Philadelphia PA 19106-3621, United States)
Abstract
Background-The Second Medicine, Angioplasty, or Surgery Study (MASS II)
included patients with multivessel coronary artery disease and normal
systolic ventricular function. Patients underwent coronary artery bypass
graft surgery (CABG, n=203), percutaneous coronary intervention (PCI,
n=205), or medical treatment alone (MT, n=203). This investigation
compares the economic outcome at 5-year follow-up of the 3 therapeutic
strategies. Methods and Results-We analyzed cumulative costs during a
5-year follow-up period. To analyze the cost-effectiveness, adjustment was
made on the cumulative costs for average event-free time and angina-free
proportion. Respectively, for event-free survival and event plus
angina-free survival, MT presented 3.79 quality-adjusted life-years and
2.07 quality-adjusted life-years; PCI presented 3.59 and 2.77
quality-adjusted life-years; and CABG demonstrated 4.4 and 2.81
quality-adjusted life-years. The event-free costs were $9071.00 for MT;
$19 967.00 for PCI; and $18 263.00 for CABG. The paired comparison of the
event-free costs showed that there was a significant difference favoring
MT versus PCI (P<0.01) and versus CABG (P<0.01) and CABG versus PCI
(P=0.01). The event-free plus angina-free costs were $16 553.00, $25
831.00, and $24 614.00, respectively. The paired comparison of the
event-free plus angina-free costs showed that there was a significant
difference favoring MT versus PCI (P=0.04), and versus CABG (P<0.001);
there was no difference between CABG and PCI (P>0.05). Conclusions-In the
long-term economic analysis, for the prevention of a composite primary end
point, MT was more cost effective than CABG, and CABG was more
cost-effective than PCI. Clinical Trial Registration
Information-www.controlled-trials.com. Registration number:
ISRCTN66068876. 2012 American Heart Association, Inc.

<12>
Accession Number
2012551522
Authors
Scheven L. De Jong P.E. Hillege H.L. Lambers Heerspink H.J. Van Pelt L.J.
Kootstra J.E. Bakker S.J.L. Gansevoort R.T.
Institution
(Scheven, De Jong, Bakker, Gansevoort) Division of Nephrology, Department
of Internal Medicine, University of Groningen, PO Box 30.001 AA53, 9700
RB, Groningen, Netherlands
(Hillege) Department of Cardiology, University Medical Center Groningen,
University of Groningen, Groningen, Netherlands
(Lambers Heerspink) Department of Clinical Pharmacology, University
Medical Center Groningen, University of Groningen, Groningen, Netherlands
(Van Pelt, Kootstra) Department of Clinical Chemistry, University Medical
Center Groningen, University of Groningen, Groningen, Netherlands
Title
High-sensitive troponin T and N-terminal pro-B type natriuretic peptide
are associated with cardiovascular events despite the cross-sectional
association with albuminuria and glomerular filtration rate.
Source
European Heart Journal. 33 (18) (pp 2272-2281), 2012. Date of Publication:
September 2012.
Publisher
Oxford University Press (Great Clarendon Street, Oxford OX2 6DP, United
Kingdom)
Abstract
Aims It has been suggested that troponins and natriuretic peptides can be
falsely elevated in subjects with impaired kidney function because of
decreased renal clearance. The value of these biomarkers in subjects with
impaired kidney function has therefore been debated. We tested in a
population-based cohort study, first, whether high-sensitive troponin T
(hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels
are cross-sectionally associated with the estimated glomerular filtration
rate (eGFR) and albuminuria, and secondly, whether these markers are
associated with cardiovascular outcome, independent of eGFR, albuminuria
and conventional cardiovascular risk factors. Methods and resultsWe
included 8121 subjects from the PREVEND study with both values of hsTnT
and NT-pro-BNP available. High-sensitive troponin T >0.01 g/L and
NT-pro-BNP >125 ng/L were defined as elevated. We first performed linear
regression analyses with hsTnT and NT-pro-BNP as dependent variables.
Next, we performed Cox-regression analyses, studying the associations of
hsTnT and NT-pro-BNP with incident cardiovascular events. Of our cohort,
6.7 had an elevated hsTnT and 12.2 an elevated NT-pro-BNP. Also, the
estimated glomerular filtration rate, albuminuria, and ECG-assessed
ischaemia and left ventricular hypertrophy were all significantly
associated with hsTnT and NT-pro-BNP in the linear regression analyses.
Both hsTnT and NT-pro-BNP appeared associated with cardiovascular events,
and these associations remained significant after adjustment for eGFR,
albuminuria, age, gender and conventional cardiovascular risk factors
(P=0.03 and P< 0.001, respectively). Only a few subjects with markedly
reduced renal function were included. The results presented are therefore
mainly valid for a population with mildly impaired renal function.
ConclusionThese data indicate that a finding of an increased hsTnT or
NT-pro-BNP in subjects with chronic kidney disease stages 1/3 should be
taken seriously as a prognostic marker for a worse cardiovascular outcome
and not be discarded as merely a reflection of decreased renal clearance.
2011 The Author.

<13>
Accession Number
2012538583
Authors
Chaudhuri A. Dandona P. Fonseca V.
Institution
(Chaudhuri) Diabetes-Endocrinology Center of Western New York, Kaleida
Health, Millard Fillmore Hospital, Buffalo, NY, United States
(Dandona) School of Medicine and Biomedical Sciences, State University of
New York at Buffalo, Buffalo, NY 14214, United States
(Fonseca) Department of Medicine, Section of Endocrinology, Tulane
University Health Sciences Center, New Orleans, LA 70112, United States
(Dandona) State University of New York, Kaleida Health, United States
Title
Cardiovascular benefits of exogenous insulin.
Source
Journal of Clinical Endocrinology and Metabolism. 97 (9) (pp 3079-3091),
2012. Date of Publication: September 2012.
Publisher
Endocrine Society (8401 Connecticut Ave. Suite 900, Chevy Chase MD 20815,
United States)
Abstract
Context: Recent studies on mediators of inflammation, experimental models
of atherosclerosis, and acute ischemia have identified novel mechanisms
through which insulin may exert cardiovascular protective effects. This
review aims to summarize current knowledge regarding the cardiovascular,
antiinflammatory, and antiatherogenic effects of insulin, and the effect
of intensive glycemic control in acute cardiovascular disease. Evidence
Acquisition: Publications of interest were identified using preselected
MeSH terminology and keywords to search online databases such as PubMed
and OVID for the period January 1988 to February 2012. Relevant
publications were obtained and reviewed by two independent observers, then
evaluated a priori against the following criteria: study quality, main
clinical outcomes, and applicability to clinical practice. Evidence
Synthesis: Insulin has been shown to exert vasodilatory, antiinflammatory,
and antiatherogenic effects in experimental models, independent of its
glucose-lowering effects. Additionally, glucose is known to exert potent
proinflammatory, prothrombotic, and proapoptotic effects during myocardial
infarct, indicative that hyperglycemia is likely to be injurious to the
heart. In this context, through its nonmetabolic and metabolic
(glucose-lowering) effects, insulin is likely to be cardioprotective and
to improve clinical outcomes in acute myocardial infarction. Conclusions:
Despite promising experimental data and evidence of benefit from
single-center randomized clinical trials, clinical evidence supporting the
cardioprotective effects of insulin from a multicenter randomized clinical
trial is still lacking. Future prospective studies with insulin infused at
adequate concentrations, individually titrated to achieve and maintain
euglycemia (blood glucose < 140 mg/dl) and minimize hypoglycemia, are
required to investigate the role of insulin in the management of patients
with acute cardiovascular disease. Copyright 2012 by The Endocrine
Society.

<14>
[Use Link to view the full text]
Accession Number
2012545698
Authors
Dikdan G.S. Mora-Esteves C. Koneru B.
Institution
(Dikdan, Mora-Esteves, Koneru) Department of Surgery, UMDNJ-New Jersey
Medical School, Medical Science Bldg, 185 South Orange Ave, Newark, NJ
07103, United States
Title
Review of randomized clinical trials of donor management and organ
preservation in deceased donors: Opportunities and issues.
Source
Transplantation. 94 (5) (pp 425-441), 2012. Date of Publication: 15 Sep
2012.
Publisher
Lippincott Williams and Wilkins (530 Walnut Street,P O Box 327,
Philadelphia PA 19106-3621, United States)
Abstract
Given the static number of deceased donors, improvements in donor
management and organ preservation to increase the number and quality of
organs transplanted per donor are more pressing. Because controlled trials
provide the best evidence, we conducted a review of English-language
literature of trials in donor management and organ preservation to provide
a compendium and to promote additional discussion and studies.Eighty-seven
reports were retrieved: 13 on hemodynamic and fluid management, 7 on
immunosuppressants, 12 on preconditioning, 34 on preservation fluids, and
21 on pulsatile perfusion. Sixteen studies are ongoing. Although hormonal
therapy is used widely, additional studies are needed to determine the
benefit of thyroid hormone and insulin replacement and to optimize steroid
regimens. Dopamine's success in reducing kidney delayed graft function
highlights the opportunity for additional preconditioning trials of remote
ischemia, gases, opioids, and others. More rapid progress requires
addressing unique barriers in consent and research approval, legal
constraints precluding research in cardiac death donors, and streamlining
collaboration of multiple stakeholders. With little interest from
industry, federal funding needs to be increased.While the University of
Wisconsin solution still reigns supreme, several promising preservative
solutions and additives with not only biophysical but also pharmacological
effects are on the cusp of phase 1 to 2 trials. After nearly three decades
of uncertainty, the recent success of a European trial has reenergized the
topic not only of machine preservation of the kidney but also of other
organs evident by trials in progress. However, the costs of such technical
innovations merit the burden of rigorous proof from controlled trials.
Copyright 2012 Lippincott Williams &Wilkins.

<15>
Accession Number
2012548190
Authors
Ranja Z. Zafar H. Ur Rasheed H.
Institution
(Ranja, Ur Rasheed) Department of Surgery and Oncollogy, Sargodha Medical
College, Sargodha, Pakistan
(Zafar) Department of Surgery CMH, Rawalpindi, Pakistan
Title
Outcome of primary reconstruction after intestinal resection in mesenteric
vascular occlusion.
Source
Pakistan Journal of Medical and Health Sciences. 4 (3) (pp 203-205), 2010.
Date of Publication: July-September 2010.
Publisher
Pakistan Journal of Medical and Health Sciences (Nila Gumbad, Lahore,
Pakistan)
Abstract
Background: primary reconstruction after resection of ischemic bowel in
mesenteric vascular occlusion involving distal ileum usually warrants
major resections. Jejuno transverse anastomosis after right hemicollectomy
is the commonly performed procedure in our unit under such setting. In
this prospective study the option of jejuno ileal anastomosis was
evaluated against jejuno transverse anastomosis. Study design: Qusi
experimental Method: this study was conducted in surgical unit II of CMH
Rawalpindi from Nov, 2005 to Dec, 2008. Patients presenting with acute
abdomen were hospitalized from emergency and out patient department. They
were operated upon with in 24 hours after fluid resuscitation and
antibiotic therapy. Patients with per-operative diagnosis of mesenteric
vascular occlusion were included in the study. The ischemic/gangrenous gut
was removed and primary anastomosis carried out. In 38 patients right
hemicollectomy with jejuno transverse anastomosis was contemplated where
as in 13 patient it was possible to establish continuity through jejuno
terminal ileal anastomosis. Post-operatively patients were put on
anti-coagulant therapy. Descriptive analysis was used for interpretation
of results. Results: A total number of n=51 patients were included in the
study, 13 in experimental group and 38 in control group. In experimental
group "A" one patient 7.69 % had infarct extension, became toxic and
tender & was re-operated on third post-operative day. The patients expired
after three days of second surgery due to cardiac event while 10 patients
26.31% died in group "B". Anastomotic leakage was observed in 5 patients
13.16% and wound infection in 7 patients 18.42% in Group "B" as compare to
0 in Group "A". The experimental group had advantage over the control
group with respect to Post-operative ileus (1.5 days and 2.5 days), time
of surgery (100 min and 150 min), length of hospital stay (mean 6 and 10
days) respectively. Institution of oral feeding was also earlier in Group
"A" 4^th Post-Op day as compare to 5.5 Post-Op day in Group "B".
Conclusion: Jejuno ileal anastomosis provides a workable option after
resection of ischemic bowel in mesenteric vascular thrombosis where
applicable. It is better tolerated by the patient in terms of morbidity
and mortality as compare to jejuno transverse anastomosis after extensive
resection.

<16>
Accession Number
70880752
Authors
Blanco R. Parras T.
Institution
(Blanco) Universidad de Santiago de Compostela, A Coruna, Spain
(Parras) Universidad de Granada, Jaen, Spain
Title
Tap-blocks are superior to epidural anesthesia after abdominal surgery.
Source
Regional Anesthesia and Pain Medicine. Conference: 31st Annual European
Society of Regional Anaesthesia, ESRA Congress 2012 Bordeaux France.
Conference Start: 20120905 Conference End: 20120908. Conference
Publication: (var.pagings). 37 (5 SUPPL. 1) (pp E136-E137), 2012. Date of
Publication: September-October 2012.
Publisher
Lippincott Williams and Wilkins
Abstract
Background and aims: Optimal analgesia is essential in major abdominal
surgery. It reduces postoperative stress response, accelerates recovery,
facilitates effective chest physiotherapy and it is imperative for an
early extubation, which may play a role in reducing postoperative
respiratory complications. A poor pain control after extensive abdominal
surgery is associated with a variety of unwanted post-operative
complications, including patient suffering, distress, confusion, chest and
heart problems, and prolonged hospital stay. Our aim is to claim the TAP
block is a better option than epidurals taking into account the settings,
safety and context around the patient in the actual climate. Methods:
There are three standard techniques to provide postoperative analgesia
after a laparotomy: epidural analgesia, patient controlled analgesia (PCA)
and TAP blocks. Although PCA with morphine can provide effective analgesia
at rest (static analgesia), it fails to provide adequate analgesia on
movement (dynamic analgesia). There is wide evidence that epidural
analgesia provides better postoperative analgesia compared with parenteral
opioids. It also enhances functional exercise capacity, health-related
quality of life, and reduces hospital stay after colonic surgery. On the
other hand epidural techniques can provide excellent analgesia but do not
reduce postoperative mortality, and although rare, there are well-known
side effects and potentially catastrophic risks to this technique
(epidural haematoma and abscess). Epidural analgesia remains the gold
standard after major surgery involving abdominal wall incision, but it is
also associated with a myriad of complications and there exists a subgroup
of patients for whom epidural insertion is contraindicated. When an
epidural fails or is contraindicated, analgesia involves large doses of
opioids which have side effects that may be poorly tolerated, causing side
effects (nausea, vomiting, constipation, sedation) and serious
complications (respiratory depression). The secondary effects of such
strategies include hypotension and respiratory depression, respectively,
and they have the potential to complicate the perioperative course in
high-risk patients with cardiorespiratory disease. Therefore, there has
been an increasing need to find effective analgesic techniques that have
lower risks. This is the case of TAP blocks The use of such blocks of the
anterior abdominal wall with local anaesthesia for postoperative analgesia
is an attractive option, because of its simplicity, safety and low cost.
Results: The TAP block is an effective method of blocking the sensory
afferents supplying theanterior-lateral abdominal wall2. The nerve
distribution in the plane has been previously described in cadaveric
dissections, and these studies suggest that lumbar blocks would be more
appropriate for lower abdominal surgeries. Injection of aniline blue 20 mL
into the lumbar TAP is likely to involve only the T10-L1 nerve roots,
implying that the lumbar technique is best suited for infraumbilical
incisions. Despite the cadaveric studies, debate remains with respect to
the somatosensory block height that can be achieved with a single local
anesthetic injection at the lumbar TAP level. ForeroMet al shows
continuous lumbar TAP block may have an analgesic role following abdominal
incisions involving not only the infraumbilical region but also
supraumbilical sites, given the extensive somatosensory block3. US-guided
TAP blocks with catheter insertion for continuous local anesthetic
infusion may be an effective alternative to epidural lumbar anesthesia in
patients with significant cardiovascular and respiratory comorbidities,
even it would be beneficial for patients with coagulation disorders in
whom neuraxial anesthesia is contraindicated. The TAP block may have less
complications and greater acceptability to patients than epidural
analgesia. Few complications following TAP blocks have been reported and
they provide both static and dynamic analgesia. There are minimal effects
on the cardiovascular system, the motor and sensory function of the lower
limbs is spared and the technique is non-sedating. These characteristics
could enhance patient deambulation and speed recovery after major surgery.
A recent study in paediatrics about the use of unilateral TAP catheters
for analgesia following single-sided open lower abdominal surgery for whom
regional analgesia was desired but an epidural catheter could not be
performed4. These series suggest that TAP catheters represent a feasible
approach to alleviate pain after lower abdominal surgery in small children
but further studies should be carried out to validate the efficacy and
safety including the comparison of TAP blocks to epidurals and intravenous
multimodal regimens. There are several approaches described to the TAP
plane, a lateral approach, an anterior approach and a lower subcostal
approach. Subcostal TAP catheters combined with PCA morphine have been
reported to be a viable alternative option to epidural analgesia in
patients undergoing upper abdominal surgery. Single shot TAP blocks have
also been used to provide analgesia in patients admitted to the ICU and as
rescue analgesia for ineffective epidural analgesia and it have been shown
to provide analgesia after lower abdominal surgery. On the other hand
comparison of continuous infusions of TAP and epidural methods has been
recently reported. The fentanyl requirements are expected to be less in
epidural patients compared with those undergoing TAP as the latter covers
only sensory dermatomes of the anterior abdominal wall. Another randomised
controlled trial study has compared the analgesic efficacy of TAP blocks
with catheter infusions versus epidural analgesia after major upper
abdominal surgery. Tramadol consumption was significantly higher in the
TAP group. This could be explained by the inability of TAP catheter
technique to cover visceral pain.Another study has found no significant
advantage of epidural analgesia over subcostal transversus abdominis plane
TAP catheter bolus analgesia. It concludes that subcostal TAP catheters
are an acceptable alternative to thoracic epidurals in patients undergoing
upper abdominal surgery. In another study published last year, three
patients in whom TAP blocks were used in our intensive care unit to
provide effective analgesia and facilitate chest physiotherapy. These case
reports demonstrate that in situations where epidural analgesia is either
contraindicated or ineffective, TAP blocks may be an effective
alternative5. Its proponents suggest that analgesia provided by the TAP
block is equal or superior to that provided by systemic opioids such as
morphine. It is also claimed that postoperative opioid consumption and
opioid-derived adverse effects can be reduced. Although the evidence is
limited to date, a recent meta-analysis of randomized trials of abdominal
surgery and the TAP block involving five studies and 236 patients, compare
with no TAP block or saline placebo, showed that this technique reduced
morphine consumption at 24 and 48 hours, but not at two hours. TAP blocks
also prolonged the time until first request for additional analgesia in
the first several hours postoperatively6. Clinical significance might be
represented by reduced adverse opioid-related side effects, such as
sedation, nausea and vomiting or pruritus, or greater patient
satisfaction. The TAP block raises some important questions, analgesia
qualities of TAP blocks in previous studies are excellent, and systemic
opioid demand was significantly decreased when compared with standard
general anaesthetic. Nevertheless, the clinical utility of transversus
abdominis plane block remains to be compared with ''gold standard''
analgesia. No studies have compared TAP block with other analgesics such
as epidural analgesia or local anaesthetic infiltration into the abdominal
wound. no study investigates TAP block without general anaesthesia, and
therefore no hard data are available regarding block qualities. For
abdominal surgery, a comparison with epidural analgesia and with
continuous lidocaine i.v. infusion is required. A recent retrospective
study included 15 patients with continuous infusions of TAP and 15 with
thoracic epidural procedures7. There was no intergroup difference for pain
score over time to 3 days for relief of either pain at rest or coughing.
Patient satisfaction was similar between the groups. No analgesic
difference was found between the two techniques. In conclusion, it
suggested that TAP block provides comparable analgesia compared with the
epidural technique, although a larger amount of supplemental fentanyl was
required by the TAP block technique. Unilateral block was recorded in two
TAP patients and patchy epidural blockade in four, requiring a modest
amount of opioid supplementation, apart from topping up. Hypotension was
recorded in two patients with epidural block but in none with TAP.
Conclusions: Transversus abdominis plane (TAP) block indications for use
of TAP block perioperatively as part of a balanced anaesthetic technique
are expanding. It is affected by multiple variables, including local
anesthetic volume, concentration, infusion time, and site of injection.
Patient factors, including height and weight, are also likely to
contribute. Large studies are required to address these
questions.Recently, the use of TAP blocks with indwelling catheters has
been described in the literature with promising results. Many relevant
studies are currently underway or awaiting publication.

<17>
Accession Number
70880748
Authors
Bonnet F. Rousset J.
Institution
(Bonnet) Anesthesie-reanimation, Assistance publique hopitaux de Paris,
Universite Pierre and Marie Curie Paris VI, Paris, France
(Rousset) Anesthesie-reanimation, Assistance publique ho pitaux de Paris,
Universite Pierre and Marie Curie Paris VIopitaux de Paris, Paris, France
Title
Regional anaesthesia in fast track surgery and rehabilitation.
Source
Regional Anesthesia and Pain Medicine. Conference: 31st Annual European
Society of Regional Anaesthesia, ESRA Congress 2012 Bordeaux France.
Conference Start: 20120905 Conference End: 20120908. Conference
Publication: (var.pagings). 37 (5 SUPPL. 1) (pp E131-E133), 2012. Date of
Publication: September-October 2012.
Publisher
Lippincott Williams and Wilkins
Abstract
Epidural analgesia has long been considered as an integral part of
rehabilitation protocols in patients scheduled for major surgery, aiming
to decrease postoperative morbidity and mortality while shortening
hospital stay. More than 10 years ago, a metaanalysis of 141 studies,
performed over a 20 years period concluded that epidural analgesia
prevented postoperative major complications and decreased postoperative
mortality (1). These results and conclusions were extensively criticized
already because one considered that changing medical practice made it
impossible to compare studies over such a long period of time. At this
time, epidural was, for example, no more considered as an effective mean
to prevent thromboembolic complications knowing that other means such as
the use of lower molecular weight heparin were much more effective. Since
2000, there has been a considerable development in endoscopic mini
invasive surgery that makes it easier and shorter postoperative
hospitalization and consequently questions the use of epidurals. Epidural
analgesia remains indeed an invasive technique with its own side effects
and complications. The question is therefore: is it worth still performing
epidural analgesia for postoperative management of patients especially
after intermediate or major surgery? The preventive effect of epidural
analgesia on postoperative pulmonary complications is mainly demonstrated
in studies published in the seventies and the eighties, when this risk was
especially high (2). Nowadays, due to prophylactic antibiotherapy, active
physiotherapy, cessation of smoking before surgery, and less invasive
surgery, the incidence of major pulmonary complications has dramatically
decreased after abdominal and thoracic surgery. The preventive role of
epidural analgesia has decreased in parallel and the
number-needed-to-treat to avoid major respiratory complication has
increased from 3-5 to more than 30 (in other words you need to use an
epidural in 30 patients to avoid one respiratory complication) (3).
Patients being more and more aged, they carry a significant amount of co
morbidities that could benefit of the use of epidurals for per and
postoperative management (4, 5). Unfortunately, the most recent
prospective trials, including a significant number of patients, have
failed to confirm the beneficial effect of epidural anaesthesia on
postoperative morbidity and mortality after major abdominal or orthopaedic
surgery most of the time (6-11). The impact of epidural analgesia on
postoperative outcome should be assessed, based on the surgical procedure.
Postoperative complications are indeed different after orthopaedic,
thoracic, and abdominal surgery. After, scheduled orthopaedic surgery,
several trials and metaanalysis have failed to document a decrease in the
incidence of cognitive dysfunction, respiratory and cardiovascular
complications in patients receiving epidural analgesia (9-11).
Nevertheless in orthopaedic surgery, regional analgesia may also provide a
functional benefit allowing a better physiotherapy. This may result in a
significant shortening of convalescence after total knee replacement (12).
A recent cohort study has assessed the impact of regional versus epidural
anaetshesia on the outcome of inpatient mortality and the secondary
outcome of repiratory and cardiovascular complications in 18,158 patients
undergoing hip fracture repair in 126 hospitals in New York in 2007 and
2008 (13). Twenty nine percent lower adjusted odds of mortality among
patients receiveing regional anaesthesoa was documented assoiatd with a
24% decrease in the odds adjusted of pulmonary complications. This study
highlights the opportunity to improve outcome through the use of regional
(mainly spinal) anaesthesia although other factors such as the delay
before surgery and the postoperative management are also critically
important. In colon surgery Basse et al. (14) combining epidural analgesia
with local anaesthetic, general anaesthesia with short acting agents,
restriction of fluid intravenous administration during surgery, careful
and less damaging as possible surgical dissection, prevention of
postoperative nausea and vomiting, lack or restricted use of nasogastric
tube, drains and bladder catheters, oral feeding with complementary
protein intake and early mobilization, they were capable of managing
patients in-hospital over less than two days after uncomplicated colon
resection. The superior quality of pain relief provided by epidural
analgesia combined with parenteral analgesia has indeed a positive impact
on out-of-bed mobilization, bowel function and consequently food intake,
that results in a significant improvement in postoperative quality of life
(15, 16). In abdominal surgery nothing compares to epidural in terms of
quality of analgesia provided. In addition epidural analgesia using local
anaesthetics offers several advantages such as a more rapid recovery in
bowel function and early deambulation. Nevertheless this objective is also
achieved by less invasive techniques such as a continuous intravenous
lidocaBne infusion (17). In addition, when using epidural anaesthesia
during surgery, there is a need for increased intravenous fluids infusion
that may compromise respiratory function and eventually the recovery of
bowel function after surgery. Epidural analgesia remains considered as the
cornerstone of rehabilitation programme supporting recovery after
abdominal surgery. It has nevertheless demonstrated that the duration of
hospital stay and postoperative morbidity are comparable with and without
epidural analgesia provided applying a multimodal rehabilitation programme
(18). In agreement after reviewing of studies concerning colon surgery,
our group has demonstrated that hospital stay was comparable with and
without epidural analgesia but it was shortened when a rehabilitation
programme was used (19). In a recent case-matched study, Lovely et al.
documented that an enhanced recovery pathway including limited intravenous
fluids and opiates and early feeding, but without epidural, duration of
hospital stay was shorter (20). Eventually continuous epidural analgesia
was demonstrated to be less cost effective than continuous wound
infiltration after abdominal surgery (21). Consequently one must confess
that it is not the use of epidural analgesia but the application of the
rehabilitation programme that is susceptible to improve the quality of
recovery after abdominal surgery. Eventually, a qualitative analysis and
three multicentre large trials, dedicated to abdominal surgery did not
documented that patients receiving epidural analgesia benefit from a more
rapid hospital discharge (18). Consequently, one is committed to consider
that epidural analgesia has no effect per se on postoperative morbidity,
but as part of a multimodal rehabilitation process it may facilitate
recovery from surgery. For laparoscopic surgery, the use of epidural
analgesia could be restricted to patients at risk of complications due to
comorbidities, and balanced with the own risk of epidural-related
complications (22). After abdominal aortic surgery, several studies have
tried to highlight a reduction in cardiovascular complications in patients
treated by epidural analgesia per and/or postoperatively, but they have
failed to achieve this goal (23-28). Nevertheless, in a selected sub-group
of patients, scheduled for abdominal aortic surgery, epidural analgesia
may occasionally reduce postoperative morbidity through a reduction in
respiratory and cardiac complications, as stressed above. During thoracic
surgery, epidural anaesthesia and analgesia is considered as the gold
standard for years. Epidural anaesthesia is especially reported to improve
respiratory function after surgery and to decrease the incidence of
pulmonary complications. Nevertheless over the past ten years,
paravertebral block has gained a growing interest. Continuous infusion of
a local anaesthetic solution on a paravertebral catheter has been
demonstrated, indeed, to provide comparable analgesia to the benefit of
fewer side effects (29). The UK pneumonectomy study was a prospective
observational cohort study in which all UK thoracic surgical centres were
invited to participate in 2005. Data were analyzed for 312 patients having
pneumonectomy at 24 UK thoracic surgical centres (30). Epidural analgesia
was used in 61% of the cases but the odds for major complications were
2.2. This may be explained by the risk of epidural related side effects
but it needs to be demonstrated in a multicentre prospective trial. In the
specific settings of cardiac surgery, epidural analgesia does not really
decrease postoperative morbidity except for respiratory complications
(31), and conveys a risk of epidural haematoma that makes numerous staff
reluctant to use it (32). Nevertheless a metaanalysis of 28 randomized
studies including 2731 patients documented a reduction in the relative
risk for mortality (0.81), for myocardial infarction (0.80) and for stroke
(0.59) but this difference was not significant due to the extremely low
incidence of these events (33). The risk ratios for respiratory
complications and arrhythmias were 0.53 and 0.68 respectively. It
therefore appears that for major events the clinical benefit of thoracic
epidural analgesia is limited but the risk of major complication of the
procedure itself including epidural haematoma may preclude its use (34).
In conclusion more than epidural itself it is the rehabilitation process
that decreases postoperative morbidity and mortality. This is to be
considered when confronting less and less invasive surgical procedures to
a less and less important clinical benefit achieved with the use of
epidurals. The balance between benefits and drawbacks must be consequently
periodically revisited for each surgical procedure.

<18>
Accession Number
70880720
Authors
Vissers K.
Institution
(Vissers) Anesthesiology, Pain en Palliative Medicine, Radboud University,
Nijmegen Medical Centre, Nijmegen, Netherlands
Title
Lumbosacral radicular pain due to disc herniation.
Source
Regional Anesthesia and Pain Medicine. Conference: 31st Annual European
Society of Regional Anaesthesia, ESRA Congress 2012 Bordeaux France.
Conference Start: 20120905 Conference End: 20120908. Conference
Publication: (var.pagings). 37 (5 SUPPL. 1) (pp E70-E72), 2012. Date of
Publication: September-October 2012.
Publisher
Lippincott Williams and Wilkins
Abstract
Lumbosacral radicular (LSR) pain is characterized by low back pain
irradiating into the leg. In patients under the age of 50 the most
important cause of LSR pain is a disc herniation. 1 Disc herniation is
commonly classified as contained or extruded herniation. Contained
herniation can be defined as a herniation with a broad base, which is
still limited within the posterior longitudinal ligament. Extruded
herniation is a herniation that breaks through this ligament. 2 Radicular
pain is thought to be caused by pressure exerted by the herniation on the
dorsal root ganglion. The nucleus pulposus material that spills onto the
dorsal root ganglion was demonstrated to induce an inflammatory reaction.
3 The dermatomal distribution of pain provides an indication for the
causative level.1 Lumbosacral radicular pain has in 60% to 80% of the
patients a favorable evolution. The pain spontaneously improves
considerably or even disappears completely within 6 to 12 weeks 2.
Diagnosis Lumbosacral radicular pain is pain that may be experienced as
sharp, piercing, throbbing or burning. Pain caused by a herniated disc
classically increases by bending forward, sitting, coughing, or
(excessive) stress on the lumbar discs and can be avoided by lying down or
sometimes by walking. 4 The most frequently used clinical test for LSR is
the Lasegue or the straight leg raising test. The patient lies in supine
position on the examination table and the examiner raises the leg. If
radicular pain can be elicited under 60-, there is a large chance that a
lumbar herniated disc is present. Though this test has a high sensitivity
the specificity is low. Magnetic resonance imaging is the preferred
medical imaging method because of the better visualization of the soft
tissue and the lower radiation dose compared to computed tomography 5 The
specificity of CT-scan and MRI is very low, because disc herniation was
found in 20% to 36% of asymptomatic patients. A resolution of the symptoms
has been reported without concordant reduction of the hernia size. 6-8
Confirmation of the level can be obtained by means of a selective
segmental nerve block. 2 The involvement of the disc should, however, be
confirmed by provocative discography, preferentially with manometric
control. 3, 9 After placement of a hollow needle into the middle of the
nucleus pulposus it is connected to a contrast delivery system which can
measure the intradiscal pressure. The patient should experience concordant
pain. The IASP and ISIS guidelines for defining discogenic pain are based
on the outcome of manometric controlled provocative discography. When the
concordant pain is produced at less than 15 psi above the opening pressure
and stimulation of two adjacent levels is not painful, it is classified as
''absolute discogenic pain''. When the concordant pain is produced at less
than 15 psi above the opening pressure and stimulation of one adjacent
level is not painful, it is classified as ''highly probable discogenic
pain''. When the concordant pain is produced at less than 50 psi above the
opening pressure and stimulation of two adjacent levels is not painful, it
is classified as ''discogenic pain''. ''Possible discogenic pain'' is
defined as elicitation of concordant pain at a pressure of less than 50
psi above the opening level and stimulation of one adjacent level is not
painful but stimulation of another disc is painful at more than 50 psi
above the opening pressure and the pain is discordant. A prospective,
match-cohort study showed that persons who underwent a discography showed
significantly greater loss of disc height in the discography group
compared to the control group at 10 years follow-up. Moreover, progression
of disc degeneration was noted in 54% of the discography group compared to
14 % in the control group. More new disc herniations were observed in the
discography group. They were disproportionally found on the side of the
annular puncture. 10 Therefore the authors recommend careful consideration
of risk and benefit when using procedures that involve disc puncture for
diagnostic and even for therapeutic reasons. Treatment Pharmacological The
natural evolution of the disease justifies a conservative approach. In the
acute phase the use of Non-Steroidal Anti-Inflammatory Drugs or Cox-2
inhibitors may be considered because of their superior effect compared
with placebo.11, 12 In case of chronic radicular pain due to disc
herniation, treatment should first try the pharmacological approach.
Because of the neuropathic character of lumbosacral radicular pain the
treatment guidelines for the pharmacological management of neuropathic
pain can be followed. 13 There is, however, little evidence specifically
for the pharmacological treatment of lumbosacral radicular pain. Epidural
corticosteroid administration The inflammatory compound of the lumbosacral
radicular pain, potentially due to leakage of nucleus pulposus material
onto the dorsal root ganglion can be managed by epidural administration of
corticosteroids, thus bringing these anti-inflammatory compound as close
as possible to the inflamed nerve root. Lumbar epidural drug
administration can be performed by the interlaminar, the transforaminal or
the caudal route. The evidence for interlaminar corticosteroid
administration was assessed in several systematic reviews. The number
needed to treat (NNT) for 50% pain reduction in the short term (1day-3
months) was calculated to be 3, for the long-term (3 months to 1 year)
however the NNT was 13.14 Two other systematic reviews also concludes that
the effect of interlaminar epidural corticosteroid administration was of
short duration.15, 16 The transforaminal approach allows a more precise
administration of the corticosteroid to the inflamed nerve root.
Randomized controlled trials show mixed results. Patients who were
scheduled for surgery were randomly assigned to receive either local
anesthetic alone or local anesthetic with corticosteroid transforaminal
epidural injections. At follow-up (13 to 28 months) 20 out of the 28
patients in the local anesthetic with corticosteroid decided not to
undergo surgery. This was the case for 9 out of the 27 patients who
received local anesthetic alone.17 In a 5-years follow-up study it was
shown that 81% of the patients who were not operated one year after the
epidural infiltration did not require surgery within the 5 years
follow-up. 18 In patients with disc herniation the transforaminal epidural
injection of corticosteroid was superior to trigger point injections.19
Patients with MRI proven disc herniation were randomly allocated to
receive transforaminal epidural local anesthetic with corticosteroid or
normal saline. At two weeks after treatment patients in the corticosteroid
group were better than in the saline group. This was, however inversed
after 3 to 6 months, because a rebound effect was observed in the
corticosteroid group.20 A sub analysis of the results of patients with a
contained herniation and those with an extruded herniation showed that in
the group with contained herniation corticosteroid injection provided
superior results to placebo while in the group with extruded herniation
the placebo group was better. 21 The three different administration
possibilities were compared in a randomized controlled trial as treatment
for patients with radicular pain due to disc herniation. The
transforaminal administration gave the better results. 22 In patients with
MRI confirmed blind interlaminar corticosteroid injection was compared to
radio-guided transforaminal injection. At 30 days the pain relief was
significantly better in the transforaminal group. Six months after
treatment patients' response to a mailed questionnaire showed better
results for transforaminal injection concerning pain, daily activities,
work and leisure activities and anxiety and depression, with a decline in
the Roland- Morris score.23 (Pulsed) radiofrequency treatment adjacent to
the dorsal root ganglion The effect of radiofrequency (RF) heat treatment
adjacent to the lumbar dorsal root ganglion was compared to sham
intervention in a well-designed randomized controlled trial. The
superiority of RF treatment could not be demonstrated. 24 Pulsed
radiofrequency treatment (PRF) is an alternative way of administering high
frequency current where each active period is followed by a silent period,
allowing the heat produced at the electrode tip to be washed out. In this
way the temperature at the electrode tip stays beneath the
neurodestructive level of 42degreeC. 25 PRF treatment adjacent to the
lumbar DRG was studied in retrospective and prospective trials for the
management of lumbosacral radicular pain. All studies showed an
improvement of the painful condition. 26, 27, 28, 29. In one study the
effect of PRF adjacent to the DRG was studied according to the etiology.
In patients with disc herniation and spinal stenosis PRF treatment
resulted in a significant pain reduction. Patients with the failed back
surgery syndrome did, however, not experience improvement. 28 Percutaneous
treatment Intradiscal injections Corticosteroids, local anesthetics,
normal saline, glucosamine, chondroitin sulfate, hypertonic dextrose and
demethylsulfoxide were injected intradiscally. The results are mixed and
do not allow formulating guidelines regarding these treatment options.9
Annuloplasty Annuloplasty uses heat application to the annulus fibrosus,
thus inducing shrinkage and repair of small annular tears, that may be
caused by small disc herniation. Besides the heat destroys newly formed
nerves in the damaged disc zone. 9 There are several ways to apply heat to
the annulus. Intradiscal electrothermal therapy (IDET) IDET uses an
thermocoil percutaneously inserted into the disc.

<19>
Accession Number
70880697
Authors
Renes S.
Institution
(Renes) Department of Anesthesiology, Radboud University, Nijmegen Medical
Centre, Nijmegen, Netherlands
Title
Adjuvants to local anesthetics in thoracic paravertebral nerve blockade.
Source
Regional Anesthesia and Pain Medicine. Conference: 31st Annual European
Society of Regional Anaesthesia, ESRA Congress 2012 Bordeaux France.
Conference Start: 20120905 Conference End: 20120908. Conference
Publication: (var.pagings). 37 (5 SUPPL. 1) (pp E30-E32), 2012. Date of
Publication: September-October 2012.
Publisher
Lippincott Williams and Wilkins
Abstract
Introduction: Adjuvants to local anesthetics have been used for more than
30 years in regional anesthesia. There are several reasons why adjuvants
are added to local anesthetis: to permit a decrease in the volume and/or
concentration of the local anesthetic (LA), prolong sensory analgesia
and/or to improve the sensory analgesia. Opioids and clonidine are the
most widely used adjuvants in regional anesthesia. Epidural opioids in
small doses may act synergistically with epidural local anesthetics in
providing analgesia. (1). However, for peripheral nerve blocks the
evidence for improving efficacy for addition of opioids is controversial
(2). Therefore the site of administering an opioid with a local
anesthetic, i.e. peripheral nerve or neuraxial, appears to be crucial for
achieving the goal of improving post-operative analgesia. Thoracic
paravertebral block is considered to be a peripheral nerve block, but a
peripheral nerve block that is performed in close proximity with the
epidural space and limited spread of discrete amounts of local anesthetic
can occur. (3) Common thoracic paravertebral block adjuvants administered
The 2 most investigated adjuvants in thoracic paravertebral block,
fentanyl and clonidine, will be further discussed. Fentanyl Opioid
receptors are present in the brain, the dorsal horn of the spinal cord,
the dorsal root ganglia and in the end terminals of primary afferent
neurons (4). When opioids are administered in peripheral nerve blocks they
can act either on the opioid receptors located on the end terminals of
primary afferent neurons or on the opioid receptors in the brain and the
dorsal horn of the spinal cord through systemic absorption. Analgesic
effect One study directly compared levobupivacaine 0.1% and a mixture of
levobupivacaine 0.05% with fentanyl 4 mug/mL for a continuous thoracic
paravertebral block in patients undergoing breast surgery under general
anesthesia; a control group received only general anesthesia. All groups
received post-operative i.v. morphine patient-controlled analgesia. (5)
Postoperative morphine consumption was significantly lower in the group
with fentanyl, but pain scores were not different between groups.
Incidence of nausea was significantly higher in the fentanyl group. A
limitation of this study was however that the morphine consumption in the
levobupivacaine 0.1% group was comparable to the morphine consumption in
the control group, which was attributed to a too low concentration of
levobupivacaine used for the continuous thoracic paravertebral infusion.
The improved analgesia in the levobupivacaine-fentanyl group could thus be
attributed to a local effect of fentanyl, a systemic effect of fentanyl or
a combination of both. Plasma levels of fentanyl in continuous thoracic
paravertebral block In 25 patients undergoing thoracic surgery with
surgically inserted thoracic paravertebral catheters serum plasma levels
of fentanyl were assessed at regular time intervals after an initial
paravertebral bolus of 100 mug followed by an infusion of fentanyl 10
mug/mL with bupivacaine 0.1% at a rate of 10-15 mL/hr. (6) At all times
interval, plasma levels of fentanyl were above the minimum effective
concentration of intravenous fentanyl administration, i.e. 0.63 ng/mL (7),
and accumulating over time. The high serum plasma levels of fentanyl would
suggest that the analgesic effect of thoracic paravertebral administered
fentanyl will be predominantly through systemic absorption, although any
local effect can not be excluded. Serum plasma levels of fentanylwere also
assessed in patients undergoing breast surgery with a continuous thoracic
paravertebral block (8). A continuous infusion of levobupivacaine 0.05%
with fentanyl 4 mug/mL at a rate of 0.15 mL/kg/hr (maximum 15 mL/hr) was
initiated after a paravertebral bolus of 50 mug fentanyl. Plasma serum
levels of fentanyl showed a trend towards accumulation and a mean maximum
plasma concentration fentanyl of 0.72 ng/mL at 24 hours was achieved.
However in all time intervals before 24 hours plasma fentanyl
concentrations were in the range of 0.38-0.43 ng/mL. A limitation of this
study is however that post-operative pain scores and post-operative
intravenous rescue morphine consumption are not reported in their study.
Nevertheless, the authors proposed that plasma fentanyl concentrations
between 0 and 24 hours would suggest that at least part of the analgesic
effect of thoracic paravertebral administered fentanyl is mediated through
a local peripheral mechanism. This proposed local effect by the authors is
probably based on their earlier study in which they found that use of the
same mixture of levobupvacaine 0.05% with fentanyl 4 mug/mL infusion
resulted in significantly lower post-operative morphine consumption in the
first 24 hours compared to the levobupivacaine 0.1% group; as stated
earlier however, the morphine consumption in the control group in this
study was comparable to morphine consumption in the levobupivacaine 0.1%
group. (5). Discussion: Serum fentanyl plasma levels of a continuous
administration of paravertebral fentanyl approach the minimum effective
concentration of intravenous fentanyl administration, which is 0.63 ng/mL
(7). A recent meta-analysis of the efficacy of paravertebral block for
postthoracotomy surgery concluded - based on indirect study comparisons -
that the addition of paravertebral fentanyl to local anesthetic does not
result in improved analgesia (9). Although serum fentanyl plasma levels of
a continuous administration of paravertebral fentanyl approach the minimum
effective concentration of intravenous fentanyl administration similar
results have been found for epidural opioid administration. Prolonged
infusion of epidural lipophilic opioids, such as fentanyl and sufentanil,
also approaches serum plasma concentration and analgesic effect comparable
to that of an intravenous infusion of these opioids alone. (10) A large
meta-analysis of post-operative epidural analgesia concluded that the
addition of opioids to local anesthetics does not result in improved
analgesia compared with local anesthetic alone.(11) Two other
meta-analyses of epidural analgesia only found weak evidence that addition
of opioid to epidural local anaesthetic may provide improved analgesia
compared to epidural local anaesthetics alone. (12-13) Conclusion:
Administration of fentanyl as an adjuvant for continuous thoracic
paravertebral block will have an analgesic effect that after prolonged
infusion will probably mediated predominantly be the result of systemic
absorption, comparable to epidural administered lipohilic opioid
administartion. A concomitant local peripheral mechanism of paravertebral
administered fentanyl analgesia however can not be excluded. In this
respect, it has been suggested that in thoracic paravertebral block the
dorsal root ganglia are probably directly affected (14) and thus part of
the analgesic effect of paravertebral fentanyl may also be attributable to
blocking the dorsal root ganglia opioid receptors. Recommendation: Based
on the limited available literature no definitive recommendation for or
against the addition of thoraic paravertebral fentanyl can be made. Adding
fentanyl in low concentrations (4 mug/mL or less) with local anesthetics
for continuous thoracic paravertebral infusion is not associated with
adverse effects, other than an increased incidence of nausea. More studies
are needed to determine whether thoracic paravertebrally administered
fentanyl may act synergistically with local anesthetics. Clonidine
Clonidine is an alpha₂-adrenoreceptor agonist; of the three
subtypes (alpha _2A, alpha _2B, and alpha
_2C) only the alpha ₂A adrenoceptor is responsible
for the anesthetic and sympatholytic responses of clonidine. (15)
alpha₂-adrenoreceptors receptors are present in the central
nervous system and the dorsal spinal cord. Although specific
alpha₂-adrenoreceptors receptors on peripheral nerves axons are
not present (16) an in vitro study has shown that high dose clonidine
blocks conduction of C and A delta fibers.(17) The presumed mechanism by
which peripheral perineural administered clonidine blocks conduction is
that clonidine prolongs the hyperpolarization-activated current, resulting
in prolongation of the hyperpolarization state of a nerve (i.e. nerve is
not susceptible for stimulation). (18) Analgesic effect Two studies
compared the effect of addition of clonidine to only a local anesthetic
continuous thoracic paravertebral infusion.(5) (19) One study found a
significant decrease in post-operative morphine consumption in patients
undergoing breast surgery when clonidine was added to the local
anesthetic, but no difference in pain scores compared to the control group
without a thoracic paravertebral catheter.(5) In patients undergoing
thoracotomy post-operative pain scores were significantly lower when
clonidine was added to the continuous thoracic paravertebral local
anesthetic infusion. (19) Both studies however also reported a significant
incidence of hypotension when clonidine was added to the thoracic
paravertebral local anesthetic infusion. (5) (19) Plasma levels of
clonidine in continuous thoracic paravertebral block One study measured
serum plasma levels of clonidine in patients patients undergoing breast
surgery with a continuous thoracic paravertebral block (8). After a
loading dose of 150 mug clonidine, a continuous infusion of
levobupivacaine 0.05% with clonidine 3 mug/mL at a rate of 0.15 mL/kg/hr
(maximum 15 mL/hr) was started. Plasma serum levels of clonidine showed a
trend towards accumulation and a mean maximum plasma concentration
clonidine of 1.74 ng/mL at 24 hours was achieved.

<20>
Accession Number
70880688
Authors
Christie I.
Institution
(Christie) Anaesthetics Department, Derriford Hospital, Plymouth, United
Kingdom
Title
Epidural analgesia after abdominal surgery: Alive and kicking or dead and
buried.
Source
Regional Anesthesia and Pain Medicine. Conference: 31st Annual European
Society of Regional Anaesthesia, ESRA Congress 2012 Bordeaux France.
Conference Start: 20120905 Conference End: 20120908. Conference
Publication: (var.pagings). 37 (5 SUPPL. 1) (pp E10-E12), 2012. Date of
Publication: September-October 2012.
Publisher
Lippincott Williams and Wilkins
Abstract
For at least 2 decades epidural analgesia has been the technique of choice
for providing pain relief after major abdominal and thoracic surgery. In
addition to having the potential to provide excellent dynamic analgesia,
epidural analgesia was claimed to reduce cardio-respiratory morbidity and
to encourage return of gastro-intestinal function. More recently, with the
introduction of Enhanced Recovery (ERAS) programmes, the place of epidural
seemed secure especially after major abdominal surgery: it seemed that no
epidural meant no ERAS. However in recent years the right of this
technique to occupy this prominent position has been questioned. Around
the world epidural analgesia appears to be in decline (1). Reasons for
this include recognition that: 1. its benefits might have been exaggerated
- the risk:benefit ratio has now moved against epidural analgesia for most
procedures, especially with the trend towards less invasive surgery 2.
there are effective alternatives which are compatible with ERAS programmes
Epidural Analgesia and Morbidity: current evidence: A number of small
trials performed during the late 1980's and 1990's suggested that epidural
analgesia after major abdominal surgery significantly reduced respiratory
and GI morbidity. In 2000 a meta-analysis of these trials appeared to
confirm the beneficial role of epidural analgesia (2) finding significant
reduction in thromboembolism, respiratory depression, pneumonia and
transfusion requirements after surgery. However this paper was quickly
followed by 2 others (3,4) which placed these findings in doubt. The
benefits of epidural analgesia appeared less than originally thought and
appeared more procedure specific. The bottom line was, while epidural
analgesia provided better pain relief, its benefits on respiratory
morbidity was limited to patients with significant pre-existing
respiratory dysfunction or following open abdominal vascular surgery. More
recent publications appear to confirm these findings. So what does the
evidence suggest now? 1. Cardiovascular morbidity: while high thoracic
epidural analgesia can increase coronary blood flow by providing a
sympathetic blockade, the benefits of this appear to be limited to a high
risk group of patients undergoing major vascular surgery (4). Even in
patients undergoing cardiac surgery, epidural analgesia does not appear to
reduce CVS morbidity (5). 2. Respiratory morbidity: in contrast to CVS,
there is consistent evidence that thoracic epidural analgesia reduces
pulmonary morbidity, especially in the relatively few high risk patients
mentioned above undergoing major surgery (6). However this does not apply
to the majority low risk patients. 3. Gastro-intestinal morbidity:
thoracic epidural analgesia has been shown to reduce the duration of ileus
following intra-abdominal surgery by around 24h when compared with
systemic opioids (7). This of course is beneficial for the early feeding
protocols of ERAS programmes. 4. Thrombo-embolic morbidity: the last
decade has seen the introduction of modern thrombo-embolic prophylaxis
tailored to individual patient requirements. Epidural analgesia does not
appear to offer any additional benefit over these measures (8). Moreover
anticoagulating a patient with an epidural catheter in situ carries an
additional risk of causing an epidural haematoma. 5. Enhanced Recovery
after Surgery (ERAS): by avoiding the ill effects of systemic opioids,
thoracic epidural analgesia has been considered a vital component of these
programmes. As ERAS may reduce complication rates by 50% and length of
stay by up to 2 days after abdominal surgery, the case for epidural
analgesia appeared to be strong. However the evidence is less clear cut. A
recent meta-analysis was unable to confirm which of the many ERAS
interventions were responsible for these benefits (9). While epidural
analgesia provides better analgesia and faster return of bowel function
after colorectal surgery, it did not shorten hospital stay but did
increase the risk of hypotension and urinary retention (10). So what does
epidural analgesia really offer us? Essentially, apart from a high risk
group where it has been conclusively shown to reduce respiratory
morbidity, we're back where we started with a technique that can provide
excellent analgesia. There is a growing opinion that this is no longer
justification enough for its routine use. This opinion is based on: 1.
Surgical techniques: surgery is becoming less invasive. Current evidence
suggests that epidural analgesia and systemic opioids provide comparable
analgesia after laparoscopic colorectal surgery (11). 2. Analgesia
Failure: epidural analgesia is very much an all-or-nothing technique:
either it provides pain relief or it doesn't. A partially working epidural
(typically an opioid + local anaesthetic mix) is arguably worse than no
analgesia as ward staff are unable to provide additional rescue opioids
because of fears of respiratory depression. In practice failure isn't
uncommon: rates of up to 30% are quoted (12). In our practice around 20%
of patients have experienced moderate or severe pain on movement during
the first 24 hours after surgery. This figure has remained fairly constant
over the last decade despite a pro-active Acute Pain Service which is
disappointing. These are complex and labour intensive techniques, and
despite training, the general surgical ward is probably not the best place
on which to manage this technique successfully. 3. Hypotension: epidural
related hypotension is common (13). In a local audit we found that 30% of
patients receiving epidural analgesia after major colorectal surgery
experienced a significant fall in blood pressure (systolic < 90mmHg for
more than 2 hours) during the 1^st 24 hours after surgery. This
is important at it has been shown that splanchnic (and therefore
anastomotic) perfusion is related to blood pressure and not flow - a
vasopressor is thus the most effective management (14). Our post operative
epidural patients are managed on Level-1 areas on the general surgical
wards. While these areas provide a greater level of monitoring,
unfortunately they do not allow for any vasopressor intervention.
Management of hypotension is therefore restricted to fluid challenging.
When this fails the next step is typically to reduce the infusion rate
until the epidural fails. Clearly this is unacceptable but providing an
extended Level-2 facility (HDU) locally is unappealing in the current
financial climate. 4. Rarer major complications of epidural analgesia: In
2009 the NAP-3 report (15) confirmed the low risk of major complications
after epidurals. The quoted risk was such that a clinician would be
unlikely to experience a complication during their working life.
Unfortunately complications seem to occur in clusters and we were on the
receiving end of such an effect. Over a 6 year period we experienced 12
major complications of post operative epidural analgesia: 6 abscesses, 3
meningitis and 3 haematomas. 3 patients were unfortunately left paraplegic
(16). Since 2006 we have had one further epidural haematoma which
fortunately did not result in spinal cord injury. So it is possible that
you may come across such a complication. Regular leg strength monitoring
which serves as a surrogate of spinal cord health is essential if patients
are not to be caused permanent harm should they be unfortunate enough to
develop one of these complications. 5. Patient satisfaction data: while
poor analgesia after surgery should be associated with poor patient
satisfaction scores, this primary outcome measure has been little studied.
Until it is, we should be reluctant to assume that analgesia alone is
enough reason to insert an epidural, especially in light of the well
documented rare but potentially catastrophic complications. Alternatives
to Epidural Analgesia So while epidural analgesia may not be indicated for
the majority of patients undergoing abdominal surgery, some form of
analgesia is still required. A systemic multimodal analgesic regimen is
good starting point but for the best chance of providing effective
analgesia a regional technique should be added. There are a number of
options: 1. IV lidocaine: a recent meta-analysis has suggested that an
intravenous infusion of lidocaine peri-operatively after abdominal surgery
reduced pain, ileus, ponv and hospital stay (17). However, given the
relatively high incidence of toxic levels, the safety of this technique on
the general surgical wards needs to be established. 2. Intrathecal
morphine: while the PROSPECT group do not recommend this technique after
abdominal surgery, a number of recent publications have demonstrated the
short term analgesic benefits of intrathecal morphine after laparoscopic
colorectal surgery (18,19). Compared with epidural analgesia, intrathecal
morphine was less effective but patients receiving this technique were
discharged home sooner after surgery (19). Controversies with this
technique include the optimal dose of morphine and where patients
receiving this technique should be monitored for the first 24 hours after
surgery.

<21>
Accession Number
70880682
Authors
Rawal N.
Institution
(Rawal) Department of Anaesthesiology and Intensive Care, University
Hospital, Orebro, Sweden
Title
Epidural technique for postoperative pain-gold standard no more?.
Source
Regional Anesthesia and Pain Medicine. Conference: 31st Annual European
Society of Regional Anaesthesia, ESRA Congress 2012 Bordeaux France.
Conference Start: 20120905 Conference End: 20120908. Conference
Publication: (var.pagings). 37 (5 SUPPL. 1) (pp E2-E4), 2012. Date of
Publication: September-October 2012.
Publisher
Lippincott Williams and Wilkins
Abstract
Epidural analgesia is a well-recognised technique for treating
postoperative pain since decades and has been generally considered the
''gold standard'' for pain management after major surgery. Studies have
shown that the technique has several additional benefits such as reduced
cardiovascular, pulmonary and gastrointestinal morbidity (1,2,3) and also
reduced mortality (4). However, more rigorous evaluation of previous data
and newer metaanalyses show less optimistic results. Epidural analgesia
and postoperative morbidity Cardiovascular morbidity: By decreasing
sympathetic outflow, thoracic epidural analgesia can improve coronary
blood flow. Current evidence suggests that thoracic epidural analgesia may
reduce the risks of cardiovascular complications such as myocardial
infarction in high-risk patients undergoing major vascular surgery.
However,there is little evidence that epidural analgesia reduces
cardiovascular morbidity in the relatively healthy ''low-risk'' surgical
population (5). The authors of a recent meta-analysis of more than 2700
cardiac surgery patients concluded that the potential benefits of TEA in
cardiac surgery may not be worth the potential risks such as neuraxial
haematoma.(6). Pulmonary morbidity: There is good evidence that epidural
analgesia is associated with reduced risk of postoperative pulmonary
complications particularly in high-risk patients undergoing open abdominal
aortic surgery or coronary artery bypass(7). However, as with
cardiovascular and gastrointestinal advantages, these benefits are seen
only when the epidural catheter is sited at the thoracic level and only
when local anaesthetics (not opioids) are used. In clinical practice the
epidural solution is typically a combination of low-dose local anaesthetic
with an opioid such as fentanyl. In general, the protective effect of
epidural analgesia against pneumonia after abdominal or thoracic surgery
has lessened over the last 35 years because of decrease in baseline risk
(8). The debate about the pulmonary benefits of epidural analgesia is
becoming increasingly irrelevant as surgical techniques become less
invasive. Gastrointestinal morbidity: Current evidence supports the use of
epidural local anaesthetics(but not opioids) to reduce the risk of
postoperative ileus(POI). A metaanalysis showed that epidural analgesia
with local anaesthetics reduced time to return of gastrointestinal
function by 24-36h compared to systemic or epidural opioids (3). However,
another metaanalysis of epidural analgesia after colorectal surgery showed
that improved analgesia and decrease in POI did not lead to shorter
duration of hospital stay (9) . There are 3 meta-analyses showing that a
continuous infusion of i.v lidocaine during and after abdominal surgery
was associated with several benefits such as reduced duration of ileus,
decreased pain scores, decreased risk of PONV and shorter hospital
stay(10,11,12). A much simpler and safer evidencebased method to prevent
or ameliorate POI is gum chewing (13). Currently, there are no comparative
studies to show that epidural is superior to either i.v lidocaine infusion
or to gum chewing in reducing the risk of POI. In a recent editorial the
authors stated ''There is a significant lack of evidence supporting the
use of epidural analgesia and we question the routine use of this mode of
analgesia in the postoperative period for patients having abdominal
surgery'' (14). Coagulation morbidity: The influence of postoperative
epidural analgesia on coagulation-related outcomes is not clear. Recent
procedure-specific metaanalyses for open aortic surgery, abdominal
surgery, THA and TKA failed to show any benefits of epidural analgesia for
reduction of coagulationrelated morbidity (15,16).A recent literature
review concluded''..in unselected patients undergoing gastrointestinal
surgery, epidural analgesia does not seem to reduce anastomotic leakage,
intraoperative blood loss, transfusion requirement, risk of
thrmboembolism, cardiac morbidity, or hospital stay compared to
conventional analgesia''(17). Length of hospital stay and the role of
epidural technique in enhanced recovery (ER) protocols: It has been
claimed that postoperative accelerated ''multimodal'' recovery programmes,
in which epidural analgesia is a key component, decrease perioperative
morbidity and reduce length of hospital stay without compromising patient
safety (18,19,20). Such protocols have been proposed for a variety of
surgical procedures, the programme for colorectal surgery is one of the
most studied and evaluated in the last decade (21). The use of thoracic
epidural analgesia using a mixture of low-dose local anaesthetics and
opioids for 48h has been recommended as one of the key elements of ER
pathways (21,22). ER strategies which include early ambulation, early
feeding, reduced use of opioid analgesia and TEA have been shown by some
investigators to lead to considerable reduction in duration of hospital
stay (27,29,31) but the results have not been widely reproduced (23).
There are a large number of ER protocols for colorectal surgery The number
of ''evidence-based'' components for such protocols can range from 4(24)
to 20 (25,26), all claim enhanced recovery and shorter stay when compared
with ''traditional care''. A Cochrane review concluded ''the quality of
the trials and lack of sufficient other outcome parameters do not justify
implementation of fast-track surgery as standard of care''(27) The debate
about the role of epidural is becoming irrelevant due to change in the
surgical technique. The PROSPECT group does not recommend epidural
technique for laparoscopic colonic surgery (28). There is a need for good
quality comparative studies to establish the critical components and
independent predictors of faster postoperative recovery in a FT programme.
In conclusion, in spite of confusion about the optimal number of
components, the implementation of ER protocols has shown impressive
reduction in hospital stays without increasing morbidity. This appears
most likely due to protocolized perioperative care rather than the
combination and number of applied ER components. Currently, there is no
convincing evidence that epidural technique as a component of such
protocols provides any further benefits, this applies to open as well as
laparoscopic colorectal surgery. Alternatives to epidural analgesia: It is
emphasised that the benefits of epidural analgesia on cardiovascular,
pulmonary and gastrointestinal morbidity have been reported in patients
undergoing open and more invasive surgery. The recommendations for
laparascopic procedures such as cholecystectomy and colonic surgery no
longer include epidural technique (28,29). Furthermore, the above
mentioned benefits of epidural analgesia were noted when compared to
systemic opioids. There is increasing evidence from several metaanalyses
and systematic reviews that good alternatives to epidural are now
available for thoracic, abdominal and major orthopaedic surgery. These
analgesic alternatives include paravertebral block (PVB) for thoracotomy
(30,31) peripheral nerve blocks for hip (32) and knee (33,34) replacement,
iv lidocaine for colorectal surgery (10,11,12), wound catheter infusions
(WCI) for a large variety of surgical procedures including abdominal,
cardiothoracic, vascular and major abdominal (35), Local Infiltration
Analgesia(LIA) technique for hip and knee joint replacement
surgery(36,37,38) and tranversus abdominis plane (TAP) block for surgery
involving abdominal wall (39). Are there no indications left for epidural
technique? There is robust data that pain relief with epidural technique
is excellent. In patients undergoing major vascular open surgery and in
high-risk patients undergoing major surgery, epidural with local
anesthetic reduces postoperative cardiovascular and pulmonary
complications . Current evidence suggests that regional anesthesia
techniques are superior to opioid analgesia. In centers where it is a
well-established routine, epidural would remain a good choice in the
transitional period while alternative evidence-based regional methods
(perineural, paravertebral, LIA, WCI, TAP blocks) are introduced into
clinical practice. In future, there might be new indications for the use
of epidural technique. There is some weak evidence that the use of
epidural technique may reduce the risk of cancer recurrence (40) and
surgical site infections (41). In conclusion, recent evidence suggests
that the benefits of epidural technique are not as impressive as believed
in the past. Although the efficacy of pain relief is outstanding and there
might be some benefits in reduced cardiovascular and pulmonary morbidity
in high-risk patients undergoing open major vascular or cardiac surgery,
in general, the indications for use of epidural technique are decreasing.
The reasons for the decline of this invasive, high-cost, labour intensive
technique are many: a) no evidence of decreased postoperative mortality b)
no convincing evidence of reduced risk of morbidity in the low- to-
medium-risk surgical population, c) advances in surgical techniques such
that many previous in-patient procedures are now day case or overnight
stay surgical procedures, d) use of fast-track, epiduralfree, early
mobilisation postoperative rehabilitation routines, e) widespread
implementation of prophylactic anticoagulant routines, f ) increasing
evidence that many less- invasive regional techniques are as good or
better than epidural after several major surgical procedures, g) no
convincing evidence of cost-effectiveness of epidural technique in spite
of use for decades, h) litigation concerns due to risk of severe
neurological complications. Thus, it is no exaggeration to say that the
diminishing role of epidural technique can be expected to continue.
Epidural technique is the gold standard for labour analgesia because there
are no good alternatives.